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Fetal Hypothalamic-Pituitary-Adrenal Stress Responses to Invasive Procedures Are Independent of Maternal Responses¹

Fetal and Neonatal Stress Research Centre (R.G., N.M.F., J.M.A.T., V.G.), Department of Maternal and Fetal Medicine, Division of Paediatrics, Obstetrics and Gynaecology, Institute of Reproductive and Developmental Biology, Imperial College School of Medicine, Hammersmith Campus, London W12 0NN, United Kingdom; and The Queen Mother’s Hospital (A.C.), Yorkhill, Glasgow G3 8SJ, United Kingdom

Address all correspondence and requests for reprints to: Rachel Gitau, Fetal and Neonatal Stress Research Centre, Department of Maternal and Fetal Medicine, Division of Paediatrics, Obstetrics and Gynaecology, Institute of Reproductive and Developmental Biology, Imperial College School of Medicine, Hammersmith Campus, London W12 0NN, United Kingdom.

	Abstract

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Paired fetal and maternal samples were obtained, at fetal blood sampling and intrauterine transfusion, to study hypothalamic-pituitary-adrenal stress responses. This confirmed that the fetus mounts an hypothalamic-pituitary-adrenal stress response to transfusion via the intrahepatic vein, which involves piercing the fetal trunk, but not to transfusion via the placental cord insertion [mean cortisol response via intrahepatic vein = 52.6 nmol/L, 95% CI (25.3–79.9), P = 0.001; mean ß-endorphin response =106 pg/mL, 95% CI (45.3–167), P = 0.002]. Baseline maternal fetal ratios were 13 [95% CI (10.7–15.2)] for cortisol and 0.8 [95% CI (0.5–1.0)] for ß-endorphin. The novel findings were: 1) that the fetal responses were independent of those of the mother, which did not change during transfusion at either site; 2) that there was a correlation between baseline fetal and maternal cortisol levels (r = 0.58, n = 51, P < 0.0001) but not between baseline fetal and maternal ß-endorphin levels, suggesting cortisol transfer across the placenta, rather than joint control by placental CRH; and 3) that fetal ß-endorphin responses were apparent from 18 weeks gestation and independent of gestational age, whereas fetal cortisol responses were apparent from 20 weeks gestation and were dependent on gestational age (y = -91.4 + 5.08x, r = 0.51; n = 16; P = 0.04; CI for slope, 0.16–10.0), consistent with the maturation of the fetal pituitary before the fetal adrenal.

	Introduction

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WE HAVE PREVIOUSLY reported that the human fetus can mount hormonal stress responses to invasive stimuli, with rises in both ß-endorphin and cortisol (1), and also noradrenaline (2). However, it is possible that responses measured in fetal plasma could be secondary to maternal responses to the stress of the transabdominal invasive intrauterine procedure. We have documented a pronounced maternal sympathetic response to fetal transfusion (2), although the lack of correlation between maternal and fetal levels suggests that there was no direct transplacental passage of noradrenaline. However, in a preliminary report (3), we have found a correlation between basal maternal and fetal plasma cortisol levels, and we suggested that this was attributable to some maternal cortisol crossing the placenta. It is therefore important to study fetal and maternal responses in parallel, which has not been done previously. The aims of this study were thus to further characterize fetal hormonal stress responses and, in particular, the relationship between the maternal and fetal hypothalamic-pituitary-adrenal (HPA) axis. We used the same ethically acceptable clinical models as in our previous studies (1, 2, 3, 4), comparing paired maternal and fetal samples after intrauterine needling at the placental cord insertion (PCI), which is not innervated and which one would not expect to be stressful for the fetus, with those at the intrahepatic vein (IHV), which has been associated with hormonal and hemodynamic fetal stress responses. One would expect both procedures to be equally stressful for the mother.

	Materials and Methods

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Patients

Women with singleton pregnancies, undergoing clinically indicated fetal blood sampling or intrauterine blood/platelet transfusion at the Center for Fetal Care, Queen Charlotte’s and Chelsea Hospital or at The Queen Mother’s Hospital, were recruited for the study. The indications for fetal blood sampling were rapid karyotyping or suspected anemia and for intrauterine transfusion, were fetal anemia or thrombocytopenia in alloimmunized pregnancies.

Fetuses were considered suitable for inclusion when the fetus was appropriately grown for gestational age and structurally normal on preprocedural ultrasound, with no evidence of hydrops, absent end-diastolic frequencies in the umbilical artery Doppler waveform, severe anemia (hemoglobin, <5 g/dL), or hypoxia [fetal pO₂ below the reference range (5)], and had a normal karyotype, to exclude conditions that can be associated with basal elevations in the study endpoints (6, 7). Fetal sex was also determined during preprocedural ultrasound and confirmed by karyotyping. Complicated procedures, involving multiple fetal vessel punctures, or when time to access the fetal circulation exceeded 10 min [shown to cause elevations in cortisol and ß-endorphin (1)], were excluded. Fifty-one fetuses satisfied the criteria for inclusion. Some of the results with cortisol have been reported previously in correspondence form (3). Twenty-three fetuses satisfied the criteria for the transfusion group.

The site of ultrasound guided fetal blood sampling or transfusion was chosen by the operator on the basis of technical factors and ease of approach, as per usual practice. Randomization of site sampling was not considered appropriate, because anatomical factors often dictate one approach in favor of the other. Neither fetal neuromuscular blockade nor analgesia was used. The mothers did not receive sedation. Intravascular transfusion was performed using packed red blood cells or platelets, warmed to body temperature before transfusion. The purity of fetal samples was confirmed by comparison of fetal and maternal mean corpuscular volumes and subsequent Kleihauer-Betke testing. Full blood count (Coulter Counter, Coulter Electronics, Luton, UK) and blood gases (Radiometer ABL 330 blood gas analyzer, Copenhagen, Denmark) were also analyzed.

Blood samples

Two milliliters of additional venous fetal blood were drawn into a heparinized syringe, after collection of clinical samples, and placed in a chilled heparinized tube. Seven milliliters of maternal blood samples were collected by venepuncture into a heparinized Vacutainer (Becton Dickinson and Co., Meylan Cedex, France) immediately before needling or transfusion, and within 10–20 min after the procedure.

Fifty microliters (500 kIU) of Trasylol/mL blood was added, immediately after collection, to all tubes. Bloods were spun in a refrigerated centrifuge at 3,000 x g to separate plasma, which was stored at -80 C until assay.

Timings

Samples were collected between 1000–1800 h, the majority (90%) between 1200–1700 h. The time from first puncture of the fetal trunk or cord until accessing the fetal circulation and collection of the first blood sample was recorded as: time to access. The duration of transfusion was recorded from the time of access until the taking of the second blood sample at the end of the transfusion. Procedures were timed using a digital stopwatch and were recorded in minutes and seconds. For analysis, times were rounded to the nearest 0.1 min. Procedures with time to access that was greater than 10 min were excluded.

Written informed consent was obtained from all the mothers, for the collection of additional blood samples for research purposes, in accordance with the Institutional Ethics Committee requirements.

Assays

Cortisol levels were assayed using a standard solid-phase RIA (by DPC, Los Angeles, CA), and maternal and fetal plasma sample pairs were analyzed in the same assay run. The lower limit of sensitivity was 10 nmol/L. The intra- and interassay coefficients of variation were 5.3% and 4.3%, respectively. Plasma levels of ß-endorphin were determined using a solid-phase two-site immunoradiometric assay (Nichols Institute Diagnostics, San Juan Capistrano, CA). The lower limit of sensitivity was 14 pg/mL, and cross-reactivity with lipotropin was 14%. The intra- and interassay coefficients of variation were 13.2% and 9.5%, respectively. In a few cases, there was insufficient sample volume to measure ß-endorphin levels as well as cortisol.

Statistics

All ranges studied were normally distributed, except for fetal ß- endorphins, time to access, and time of transfusion, which were normalized by log transformation. Data were analyzed by standard parametric statistics using SPSS, Inc. 9.0 for Windows (Chicago, IL).

	Results

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Patient details are given in Table 1.

There was no significant correlation between basal concentrations of either fetal or maternal cortisol and gestational age, over the range studied (17–35 weeks), nor was there with fetal ß-endorphin. However, maternal basal ß-endorphin rose significantly with advancing gestational age [y = -17.7 + 2.20x; r = 0.36; n = 37; P = 0.03; 95% confidence interval (CI) for slope, 0.27–4.13] (Table 2). There was no correlation between maternal or fetal basal values and time of day. There was no difference in basal fetal values by sex of the fetus for either cortisol [mean (95% CI): males = 48.3 (42.2–54.4), n = 24; females = 52.3 (40.5–64.1), n = 15] or ß-endorphin [geometric mean (95% CI): males = 72.9 (53.2–99.5), n = 22; females = 74.6 (51.9–104), n = 15].

View larger version (16K): [in this window] [in a new window]   Figure 1. a, Correlation between basal maternal and fetal plasma cortisol levels (y = 19.5 + 0.05x; r = 0.58; n = 51; P < 0.0001; 95% CI for slope, 0.03–0.07. b, Correlation between basal maternal and fetal plasma ß-endorphin levels (r = -0.2, n = 36, ns).

View larger version (15K): [in this window] [in a new window]   Figure 2. a, Correlation between basal fetal plasma cortisol and time to access the fetal IHV (r = 0.2, n = 31, ns). b, Correlation between basal fetal plasma ß-endorphin and time to access the fetal IHV (y = 44.7 + 11.5x; r = 0.56; n = 29; P = 0.001; 95% CI for slope, 4.84–18.2).

There was a significant correlation between maternal baseline cortisol and ß-endorphin levels (r = 0.52, n = 35, P = 0.002). There was no such correlation between fetal baseline levels (r = 0.048, n = 46, ns).

Fetal responses

Several fetuses required multiple transfusions at the same site; in these cases, the first transfusion at each site was used.

Pretransfusion cortisol and ß-endorphin levels were similar in the IHV and PCI groups (Table 1). Figure 3 shows that transfusion resulted in a significant rise in fetal plasma cortisol levels when carried out at the IHV [mean , 52.6 nmol/L; 95% CI (25.3–79.9); P = 0.001] but not when the same procedure was done via the PCI [mean , 3.27 nmol/L; 95% CI (-13.5 to 20.1); P = 0.7]. Similarly, there was a fetal ß- endorphin response to IHV transfusion [mean , 106 pg/mL; 95% CI (45.3–167); P = 0.002] but not to PCI transfusion [mean , 12.2 pg/mL; 95% CI (-11.9 to 36.3); P = 0.3].

View larger version (29K): [in this window] [in a new window]   Figure 3. Fetal plasma cortisol and ß-endorphin concentrations before and after transfusion at the IHV and the PCI.

The magnitude of the cortisol response at the IHV increased with gestational age (y = -91.4 + 5.08x; r = 0.51; n = 16; P = 0.04; 95% CI for slope, 0.16–9.99); there was no such correlation between the ß-endorphin response and gestational age (r = 0.03, n = 14, ns) (Fig. 4 and Table 2).

View larger version (10K): [in this window] [in a new window]   Figure 4. Fetal cortisol and ß-endorphin responses to transfusion at the IHV, as a function of gestational age. Cortisol y = -91.4 + 5.08x; r = 0.51; n = 16; P = 0.04; 95% CI for slope, 0.16–9.99. ß-endorphin, r = 0.03, n = 14, ns.

Paired pre- and posttransfusion maternal samples were available for 7 IHV and 5 PCI procedures. Maternal cortisol and ß-endorphin levels did not change with transfusion [mean s, 28.9 nmol/L (95% CI, -60.7 to 119) and 5.82 pg/mL (95% CI, -6.08 to 17.7), respectively (Fig 5)]. values were similar in IHV and PCI transfusions. This lack of response was equally apparent at all gestational ages studied (range, 22–35 weeks). There was no relationship between paired maternal and fetal cortisol or ß-endorphin.

View larger version (13K): [in this window] [in a new window]   Figure 5. Maternal plasma cortisol and ß-endorphin concentrations before and after transfusion. •, IHV; , PCI.

	Discussion

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The finding of a positive correlation between basal maternal and fetal cortisol confirms and extends our pilot study (3). There was no similar correlation in ß-endorphin levels. This suggests that the cortisol correlation is unlikely to be caused by joint control via placental CRH release into both maternal and fetal compartments, because then, one would expect other POMC derivatives (such as ß -endorphin) also to be correlated. Indeed, Schulte et al. (8) have shown that CRH that is administered to the mother in the third trimester of pregnancy does not increase maternal cortisol.

It has been suggested that high levels of placental 11ß-hydroxysteroid-dehydrogenase type 2 activity excludes maternal cortisol from the fetus (9, 10). A direct study of maternal-fetal cortisol transfer in the fetal-placental unit before abortion showed that 15% of ³H-cortisol crossed the placenta unmetabolized (11). Our finding is compatible with substantial (80–90%) metabolism of maternal cortisol during passage through the placenta. Because fetal levels are about 13-fold lower than maternal, a rise of 10–20% in maternal levels could still double fetal concentrations. Our results indicate that 33.5% of the variance in fetal cortisol is attributable to maternal levels.

If there is direct transfer of maternal cortisol across the placenta in sufficient concentration to have a functional effect on the fetus, this provides a mechanism by which antenatal maternal stress may affect the fetus. Maternal stress in pregnancy has been shown to be associated with babies with lower birth weight and impaired brain development (12). Numerous animal studies have linked antenatal maternal stress with altered long-term hyperreactive HPA responses in the resultant offspring (13). The effects of maternal stress on the fetus can thus have long-term implications (14). The results presented here suggest that a mechanism of direct transfer occurs in humans, so that maternal stress, which results in elevated cortisol levels, may have a direct effect on development.

The correlation between maternal and fetal cortisol levels, suggesting that maternal cortisol may be transported to the fetus, raises a question about the independence of the fetal stress response to IHV transfusions. However, the fact that maternal levels of cortisol and ß-endorphin did not change with transfusion to the fetus at either site (Fig. 5) suggests that maternal responses did not influence the fetal responses described here. It may seem surprising that mothers did not show any activation of the HPA axis after what one would expect to be a stressful procedure for her also (i.e. having a 20-gauge needle inserted under local anesthetic through her abdomen into the fetal circulation, along with a small procedure-related risk of miscarriage and fetal death). Indeed these procedures are known to elicit a noradrenaline response in the mother (2). However, others have observed a desensitization of the maternal HPA axis response during pregnancy (8), which may, in part, be caused by release of large amounts of CRH from the placenta (15). Even though maternal cortisol levels have been shown to be increased during pregnancy by stressful experiences (8, 16), it may be that a greater insult is needed to achieve the same effect as in the nonpregnant state. Alternatively, it is also possible that the mother was stressed in anticipation of the procedure and, so, was resistant to further HPA activation by the procedure itself.

The youngest fetus in the previous study was 23 weeks old (1), whereas the present study included fetuses at earlier gestational ages. A fetus at 20 weeks showed a typically large response. This is of interest because it has been suggested that the human fetal adrenal cortex cannot synthesize cortisol de novo before 24 weeks (17). However, the fetus at 18 weeks did not show a cortisol response, but he did show a rise in ß-endorphin. The finding that the cortisol response was significantly related to gestational age in the range from 18–35 weeks but that the ß-endorphin response was not, and was actually negative (Table 2, Fig. 4), suggests that the ß- endorphin response from the fetal pituitary may mature before the cortisol response from the fetal adrenal. However, it must be noted that the significant cortisol correlation (Fig. 4a) depends on a relatively small number of samples and should thus be interpreted with caution.

Earlier maturation of the pituitary could explain why basal fetal ß-endorphin levels are higher than those of the mother (maternal/fetal ratio, 0.8), whereas cortisol values are much lower (maternal/fetal ratio, 13). In this context, it would be of interest also to examine basal fetal and maternal ACTH levels and responses. Because of the small volumes of fetal blood available, it was not possible to do this in the present study.

Basal fetal ß-endorphin levels correlated with time of needling access to the IHV (Fig. 2b), something not found in our smaller earlier study (1). A fetal cortisol link with time became apparent only in the current study, only in complicated procedures in which access needling lasted more than 10 min (unpublished observations). This supports the hypothesis that the ß-endorphin response is controlled by the fetal pituitary and thus is more rapid than the adrenal response; again, this should be interpreted with caution in view of the relatively small numbers of such fetal procedures.

Ours are the first studies of human fetal HPA responsiveness in vivo. Others have looked at basal levels of cortisol and ß-endorphin, and some have examined paired maternal and fetal samples, although not in the same cohort. The finding of no relationship between basal fetal cortisol concentrations and gestational age between 17–35 weeks is similar to the results of Economides et al. (18) but in contrast to Donaldson et al. (16). However, the rise found by the latter group was predominantly in late gestation. The exact gestational period under study is important, because there could still be a rise in the last 4 weeks of pregnancy and in the first trimester (19), periods not included in the present study.

Only one previous study has compared maternal and fetal ß-endorphin plasma levels during pregnancy and has found that fetal values were higher than maternal (20). Unlike our study, Rudunovic et al. (20 did find a correlation between maternal and fetal ß-endorphin values but over a wider gestational age range, from 18–39 weeks). Our results are in agreement with those of Goland et al. (21), who similarly did not find any correlation in maternal and fetal ß-endorphin in cord blood at delivery. Radunovic et al. (22) found that basal fetal ß-endorphin increased with fetal blood sampling at the PCI but only when multiple punctures were required and time to access the vein exceeded 3 min. In contrast, we found no evidence for a ß-endorphin response to needling at the PCI in uncomplicated procedures.

In conclusion, in the human fetus, the HPA axis seems functional from midgestation. Although there is a correlation between basal fetal and maternal cortisol levels, suggesting some placental transfer, the fetal stress responses, demonstrated in response to transfusion at the IHV, are independent of those of the mother.

	Acknowledgments

 
We acknowledge equipment support from the Children Nationwide Medical Research Foundation and the John Ellerman Foundation.

	Footnotes

 
¹ Funded by a project grant from Wellbeing. The Fetal and Neonatal Stress Research Center receives infrastructural support from the Henry Smith Charity.

Received January 24, 2000.

Revised June 5, 2000.

Revised September 1, 2000.

Accepted September 8, 2000.

	References

Top Abstract Introduction Materials and Methods Results Discussion References

 

1. Giannakoulopoulos X, Sepulveda W, Kourtis P, Glover V, Fisk NM. 1994 Fetal plasma cortisol and ß-endorphin response to intrauterine needling. Lancet. 344:77–81.[CrossRef][Medline]
2. Giannakoulopoulos X, Teixeira J, Glover V, Fisk N. 1999 Human fetal and maternal noradrenaline responses to invasive procedures. Pediatr Res. 45:494–499.[Medline]
3. Gitau R, Cameron A, Fisk NM, Glover V. 1998 Fetal exposure to maternal cortisol (letter). Lancet. 352:707–708.[CrossRef][Medline]
4. Teixeira JM, Glover V, Fisk NM. 1999 Acute cerebral redistribution in response to invasive procedures in the human fetus. Am J Obstet Gynecol. 181:1018–1025.[CrossRef][Medline]
5. Nicolaides KH, Economides DL, Soothill PW. 1989 Blood gases, pH, and lactate in appropriate- and small-for-gestational-age fetuses. Am J Obstet Gynecol. 161:996–1001.[Medline]
6. Ruth V, Hallman M, Laatikainen T. 1993 Corticotropin-releasing hormone and cortisol in cord plasma in relation to gestational age, labour, and fetal distress. Am J Perinatol. 10:115–118.[Medline]
7. Wardlaw SL, Stark RI, Baxi L, Frantz AG. 1979 Plasma ß-endorphin and ß-lipotropin in the human fetus at delivery: correlation with arterial pH and pO2. J Clin Endocrinol Metab. 49:888–891.[Abstract]
8. Schulte HM, Weisner D, Allolio B. 1990 The corticotrophin releasing hormone test in late pregnancy: lack of adrenocorticotrophin and cortisol response. Clin Endocrinol (Oxf). 33:99–106.[Medline]
9. Lopez-Bernal A, Flint APF, Anderson ABM, Turnbull AC. 1980 11ß-hydroxysteroid dehydrogenase activity in human placenta and decidua. J Steroid Biochem. 13:1081–1087.[CrossRef][Medline]
10. Seckl J. 1993 11ß-Hydroxysteroid dehydrogenase isoforms and their implications for blood pressure regulation. Eur J Clin Invest. 23:589–601.[Medline]
11. Murphy BEP, Clark SJ, Donald IR, Pinsky M, Vedady D. 1974 Conversion of maternal cortisol to cortisone during placental transfer to the human fetus. Am J Obstet Gynecol. 118:538–541.[Medline]
12. Lou H, Hansen D, Nordentoft M, et al. 1994 Prenatal stressors of human life affect fetal brain development. Dev Med Child Neurol. 36:826–832.[Medline]
13. Clarke AS, Schneider ML. 1993 Prenatal stress has long-term effects on behavioural responses to stress in juvenile rhesus monkeys. Dev Psychobiol. 26:293–304.[CrossRef][Medline]
14. Sapolsky RM. 1996 Why stress is bad for your brain. Science. 273:749–750.[CrossRef][Medline]
15. Petraglia F, Potter E, Cameron VA, et al. 1993 Corticotropin-releasing factor-binding protein is produced by human placenta and intrauterine tissues. J Clin Endocrinol Metab. 77:919–924.[Abstract]
16. Donaldson A, Nicolini U, Symes EK, Rodeck CH, Tannirandorn Y. 1991 Changes in concentrations of cortisol, dehydroepiandrosterone sulphate and progesterone in fetal and maternal serum during pregnancy. Clin Endocrinol (Oxf). 35:447–451.[Medline]
17. Mesiano S, Jaffe RB. 1997 Developmental and functional biology of the primate fetal adrenal cortex. Endocr Rev. 18:378–403.[Abstract/Free Full Text]
18. Economides DL, Nicolaides KH, Linton EA, Perry LA, Chard T. 1988 Plasma cortisol and adrenocorticotropin in appropriate and small for gestational age fetuses. Fetal Ther. 3:158–164.[Medline]
19. Murphy BEP. 1982 Human fetal serum cortisol levels related to gestational age: evidence of a midgestational fall and a steep late gestational rise, independent of sex or mode of delivery. Am J Obstet Gynecol. 144:276–282.[Medline]
20. Radunovic N, Lockwood CJ, Alvarez M, Nastic D, Berkowitz RL. 1992 ß- Endorphin concentrations in fetal blood during the second half of pregnancy. Am J Obstet Gynecol. 167:740–744.[Medline]
21. Goland RS, Wardlaw SL, Stark RI, Frantz AG. 1981 Human plasma ß- endorphin during pregnancy, labour, and delivery. J Clin Endocrinol Metab. 52:74–78.[Abstract]
22. Radunovic N, Lockwood CJ, Ghidini A, Alvarez M, Berkowitz RL. 1993 Is fetal blood sampling associated with increased ß-endorphin release into the fetal circulation? Am J Perinatol. 10:112–114.[Medline]

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This Article Abstract Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gitau, R. Articles by Glover, V. Search for Related Content PubMed PubMed Citation Articles by Gitau, R. Articles by Glover, V. Pubmed/NCBI databases Medline Plus Health Information Blood Transfusion and Donation High Risk Pregnancy Pregnancy Stress